Pbx homeodomain proteins pattern both the zebrafish retina and tectum

<p>Abstract</p> <p>Background</p> <p><it>Pbx </it>genes encode TALE class homeodomain transcription factors that pattern the developing neural tube, pancreas, and blood. Within the hindbrain, Pbx cooperates with Hox proteins to regulate rhombomere segment identity. Pbx cooperates with Eng to regulate midbrain-hindbrain boundary maintenance, and with MyoD to control fast muscle cell differentiation. Although previous results have demonstrated that Pbx is required for proper eye size, functions in regulating retinal cell identity and patterning have not yet been examined.</p> <p>Results</p> <p>Analysis of retinal ganglion cell axon pathfinding and outgrowth in <it>pbx2/4 </it>null embryos demonstrated a key role for <it>pbx </it>genes in regulating neural cell behavior. To identify Pbx-dependent genes involved in regulating retino-tectal pathfinding, we conducted a microarray screen for Pbx-dependent transcripts in zebrafish, and detected genes that are specifically expressed in the eye and tectum. A subset of Pbx-dependent retinal transcripts delineate specific domains in the dorso-temporal lobe of the developing retina. Furthermore, we determined that some Pbx-dependent transcripts also require Meis1 and Gdf6a function. Since <it>gdf6a </it>expression is also dependent on Pbx, we propose a model in which Pbx proteins regulate expression of the growth factor <it>gdf6a</it>, which in turn regulates patterning of the dorso-temporal lobe of the retina. This, in concert with aberrant tectal patterning in <it>pbx2/4 </it>null embryos, may lead to the observed defects in RGC outgrowth.</p> <p>Conclusion</p> <p>These data define a novel role for Pbx in patterning the vertebrate retina and tectum in a manner required for proper retinal ganglion cell axon outgrowth.</p

On the Fine Structure of the Nematocysts in the Pianula Larva of a Sea Anemone,Anthoplura elegantissima

[[volume]]18

Gene expression analysis via hybridization shows altered expression of Pbx dependent transcripts in null embryos

<p><b>Copyright information:</b></p><p>Taken from "Pbx homeodomain proteins pattern both the zebrafish retina and tectum"</p><p>http://www.biomedcentral.com/1471-213X/7/85</p><p>BMC Developmental Biology 2007;7():85-85.</p><p>Published online 16 Jul 2007</p><p>PMCID:PMC1934912.</p><p></p> The expression of , , and is reduced in null embryos (B, F, and J), when compared to wild type (A, E, and I) at 18 hpf. At 24 hpf, and show reduced expression in null embryos (D and H) when compared to wildtype (C and G), while the expression of is unaffected (K and L). The expression of is limited to the RPE at the periphery of the eye in wild type embryos at 24 hpf (M), and is expanded to the posterior retina in null embryos (N). All embryos were hybridized with the probe indicated, as well as , as an indicator of the level of Pbx function

The laminar structure of null eyes is normal after 5 days of development

<p><b>Copyright information:</b></p><p>Taken from "Pbx homeodomain proteins pattern both the zebrafish retina and tectum"</p><p>http://www.biomedcentral.com/1471-213X/7/85</p><p>BMC Developmental Biology 2007;7():85-85.</p><p>Published online 16 Jul 2007</p><p>PMCID:PMC1934912.</p><p></p> All laminar layers are present and in both wild type (A and B) and, and mutants injected with morpholinos (D and E). We note a consistent decrease in eye size in null embryos, but the proportion of eye area occupied by the retinal pigmented epithelium in morphants is significantly increased (F verses C). The relative position of the optic nerve is similar in both wild type and morphant embryos. The retinal photoreceptor layer is absent in the ventral domain of the eye in mutants injected with morpholinos (I) when compared to wildtype (G) and is disorganized (compare H, wildtype, with J, mutants injected with morpholinos). Photoreceptor labeling was accomplished using the zpr-1 monoclonal antibody

Is genetically downstream of and is necessary for expression of genes in the dorsal/temporal retina

<p><b>Copyright information:</b></p><p>Taken from "Pbx homeodomain proteins pattern both the zebrafish retina and tectum"</p><p>http://www.biomedcentral.com/1471-213X/7/85</p><p>BMC Developmental Biology 2007;7():85-85.</p><p>Published online 16 Jul 2007</p><p>PMCID:PMC1934912.</p><p></p> Expression of is strongly reduced in null embryos (B), when compared with wildtype (A) at 24 hpf. Knockdown of results in a loss of and expression (D and F) when compared with wildtype (C and E). null embryos were also hybridized with as well as , as a marker of function

GDF6, a Novel Locus for a Spectrum of Ocular Developmental Anomalies

Colobomata represent visually impairing ocular closure defects that are associated with a diverse range of developmental anomalies. Characterization of a chromosome 8q21.2-q22.1 segmental deletion in a patient with chorioretinal coloboma revealed elements of nonallelic homologous recombination and nonhomologous end joining. This genomic architecture extends the range of chromosomal rearrangements associated with human disease and indicates that a broader spectrum of human chromosomal rearrangements may use coupled homologous and nonhomologous mechanisms. We also demonstrate that the segmental deletion encompasses GDF6, encoding a member of the bone-morphogenetic protein family, and that inhibition of gdf6a in a model organism accurately recapitulates the proband’s phenotype. The spectrum of disorders generated by morpholino inhibition and the more severe defects (microphthalmia and anophthalmia) observed at higher doses illustrate the key role of GDF6 in ocular development. These results underscore the value of integrated clinical and molecular investigation of patients with chromosomal anomalies